Miércoles 12 de Noviembre de 2008, Ip nº 254

The Mason's apprentice
Por Pz Myers

No one wants to be an architect because they're interested in the physics of nails and screws and glue and mortar. But as stirring as it can be to contemplate a great piece of architecture — it's easy to imagine Brunelleschi's excitement as he first contemplated the stunning dome he was to build on Florence's Basilica di Santa Maria del Fiore — and as much fun as it can be to design a dream house, no architect will ever realize a vision without an understanding of how to join a structure's materials.

Biology has a similar problem. Much of modern developmental biology has a bias for grand visions of form and structure. Our major model organisms are creatures like fruit flies and mice and zebrafish, but these are the elaborate edifices of evolution, far out on the extreme edge of multicellular complexity. While it is both interesting and productive to study the grand patterns of development in producing such wonderful phenomena as the outline of the body plan in the expression of Hox genes, or the growth of limbs, or the functional anatomy and physiology of intricate sensory organs like the eye, these processes all hinge on the most fundamental pieces of ontogeny: the mechanisms by which cells can adhere, interact, and cooperate. These are the nails and glue of the development and evolution of multicellular organisms. And, just as Brunelleschi's greatest achievement began not with a grand plan, but with expert knowledge of the simple brick, we can better understand those processes if we look away from the mice and turn our eyes to simpler, humbler creatures, ones that have mastered the crucial skills of cellular masonry.

Multicellularity requires complex cell adhesion and signaling abilities — development and differentiation cannot occur without them. A multicellular organism is made up of cells that stick to one another with varying degrees of strength, which is mediated by an external coat of proteins and sugars that makes cells sticky in specific ways. In addition, cells secrete proteins and sugars that form a kind of fibrous goo called the extracellular matrix, to which they can also stick. When cell proteins bind to other cells or the extracellular matrix, the proteins trigger biochemical changes — the signaling part of the process — that can cause changes in cell metabolism, gene activity, cell shape, and physiology. These capabilities are fundamental to building a multicellular organism.

So where did they come from?

One must be careful when investigating this question not to make an easy but erroneous assumption: that cell adhesion and cell-to-cell signaling are a consequence of multicellularity. They are not. In fact, it turns out that single-celled organisms have a diverse array of mechanisms for interacting with one another, and multicellular life's fancy cell-communication tools are recent appropriations of mechanisms refined by evolution over billions of years, well before the first tiny worm congealed in the late pre-Cambrian.

"Simple" one-celled organisms like bacteria (which aren't simple, except in terms of number of cells) are sensitive to their environment, including the presence of other bacteria, and transduce chemical signals around them into changes in gene activity. The central principles of cell signaling are all in place in E. coli, and we can see the general idea clearly expressed in the rest of the prokaryotes. But another group of single-celled organisms, a group of eukaryotes — are of particular interest to multicellular animals like ourselves because they are the protists most closely related to us. These organisms are pf great interest to evolutionary biologists because they demonstrate that our toolbox of cell-adhesion and signaling proteins are of utility to organisms that don't have tissues and a higher level of organization. These fascinating creatures are the choanoflagellates.

Choanoflagellates have a distinctive form: a cell with an apical flagellum, a kind of propeller that can move it through the water or drive a flow of water over it, and a ring or collar of microvilli, thin projections that act like a net to capture bacteria for food. Choanoflagellates were initially suspected of being distant relatives of multicellular animals because of their similarity to cells called choanocytes in sponges —  slice into a living sponge, put the section on a microscope, and what you'll see are many cells that look just like choanoflagellates press-ganged into the lining of the network of tubes in the sponge, flailing their flagella to drive water through the animal and using their collar of microvilli to filter out small food particles. The recent sequencing of the choanoflagellate genome has further confirmed their affinities to us, revealing that they share an amazingly rich repertoire of cell adhesion and signaling molecules with us.

Two particularly significant classes of proteins that animals use for adhesion and signaling are shared between animals and choanoflagellates. One is a group of proteins called cadherins. These are important cell-adhesion molecules that are regulated by calcium in the environment. Before being found in choanoflagellates, cadherins were thought to be unique to animals — plants and fungi do not have them. Another is a group of proteins called integrins that help cells stick to the extracellular matrix. Among other things, these molecules adhere to the collagen in connective tissues; they are essential for holding us together in a coherent form, versus a pile of gooey jelly.

At first, learning that we share those proteins with choanoflagellates might seem something like making the entirely unsurprising discovery that the brick walls of a one-room house are held together by the same stuff as Brunelleschi's dome. There are differences between the two structures, obviously, but the mechanism unites them; so, too, with animals and choanoflagellates. But the discovery of our shared molecular heritage is far more revealing than that. Adhesion to an extracellular matrix is one of the key innovations of animal evolution and animals also use these molecules to regulate cell sorting and migration, to establish different domains of gene expression, and to set up polarity. So, understanding how choanoflagellates use such an assortment of sophisticated molecules to regulate their interactions can tell us how multicellularity evolved.

Cooperation is one part of the story. Some species of choanoflagellate are colonial, others are solitary, and others switch as circumstances demand between aggregating with others or living as free-swimming forms. Alone, these organisms can use their collars to harvest bacteria, but together they can form larger, more efficient feeding colonies. The ability to adhere to extracellular proteins and sugars is a product of two phenomena: Choanoflagellates will attach to external substrates in order to stay in place, and to their bacterial prey in order to catch them. The increasing elaboration of molecules to sense and adhere for the purpose of colony formation and feeding became the foundation for the specialization and coherent patterning that is the hallmark of animal organization; as from humble brick and mortar, soaring cathedrals can be built, so too do the kinds of global integration and sophisticated cellular networking that we take for granted have their roots in short-term utilitarian connectedness in microbes.

  24/10/2008. Seed Magazine.